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Updated: Jul 13, 2026
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
Macrophage-induced muscle pathology results in morbidity and mortality for Ross River virus-infected mice
B A Lidbury1, C Simeonovic, G E Maxwell
1Gadi Research Centre, Division of Science and Design, University of Canberra, Canberra, Australia.
Abstract:
Ross River virus (RRV) is an Australian alphavirus that is often responsible for chronic epidemic polyarthritis and myalgia in humans. Past studies have shown severe disruption of striated muscle fibers to be prominent in RRV pathology in mice; in the present study, macrophages were directly implicated as the primary mediators of muscle damage. General immunosuppressive therapies had only minor effects on mortality and morbidity in RRV-infected mice, with no inhibition of muscle damage. Treatment of mice with macrophage-toxic agents (e.g., silica) prior to RRV infection completely abrogated disease symptoms without significantly affecting titers of virus in organs. Further studies found that clinical signs of infection and muscle damage correlated with a massive influx of macrophages into hind leg muscle, whereas no such infiltrate or damage was observed for silica-treated mice. These observations are significant for the human disease context, as monocytic cells have been detected in the synovial effusions of persons with epidemic polyarthritis.
Insights
Ross River virus (RRV) causes epidemic polyarthritis. Macrophages, not the virus itself, mediate muscle damage in mice, suggesting new therapeutic targets for RRV infection.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Ross River virus (RRV) is an Australian alphavirus causing epidemic polyarthritis and myalgia.
- Previous studies indicated significant striated muscle fiber disruption in RRV-infected mice.
- The specific cellular mechanisms driving RRV-induced muscle pathology remained unclear.
Purpose of the Study:
- To investigate the role of macrophages in Ross River virus-induced muscle damage.
- To evaluate the efficacy of targeting macrophages in mitigating RRV pathology.
Main Methods:
- Infection of mice with Ross River virus.
- Administration of general immunosuppressive agents.
- Treatment with macrophage-toxic agents (silica) prior to infection.
- Assessment of clinical signs, mortality, morbidity, viral titers, and muscle histology.
Main Results:
- Macrophages were identified as the primary mediators of striated muscle fiber damage in RRV infection.
- Macrophage depletion using silica abrogated disease symptoms and muscle damage without affecting viral loads.
- General immunosuppressive therapies showed minimal impact on RRV disease progression and muscle damage.
Conclusions:
- Macrophages play a critical role in the pathogenesis of Ross River virus-induced muscle disease.
- Targeting macrophages presents a potential therapeutic strategy for managing Ross River virus infections.
- These findings have implications for understanding human epidemic polyarthritis, where monocytic cells are found in affected joints.
